Elevation of urinary βig-h3, transforming growth factor-β-induced protein in patients with type 2 diabetes and nephropathy

Transforming growth factor-beta (TGF-beta) is a pro-sclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. betaig-h3 is an extracellular matrix protein which is induced in many cells by TGF-beta. This study examined urinary betaig-h3 excretion in diabetic patients with elevated urinary albumin excretion and the clinical application of urinary betaig-h3 as a marker of diabetic nephropathy. Urinary and serum betaig-h3 levels were determined by enzyme-linked immunosorbent assay in 163 type 2 diabetic patients and 101 healthy control subjects of comparable age and weight. The ratio of urinary betaig-h3 and TGF-beta to creatinine was analyzed in patients with different degree of nephropathy. The betaig-h3 to creatinine ratio in urine was elevated in all groups of type 2 diabetics with normoalbuminuria (101.6 +/- 9.27), microalbuminuria (120.2 +/- 14.48), and overt proteinuria (146.3 +/- 16.34), when compared with control subjects (64.8 +/- 7.14) (P0.01). There was a positive correlation between urinary betaig-h3 and TGF-beta excretion rate and a positive correlation between urinary betaig-h3 and albumin excretion rate (AER). These data show that urinary levels of betaig-h3 are elevated in type 2 diabetic patients with nephropathy and may be used as a marker of diabetic nephropathy.